Scientists Go Long to Navigate C9orf72 Repeat Sequences

Charting C9 Territory. An emerging long-read next-generation sequencing method enabled researchers to identify and closely estimate the number of repeats in the C9orf72 gene, and capture the sequence of at least a large part of this repeat-rich region in one person with the disease. [Courtesy of Ebbert et al., 2018, Molecular Neurodegeneration. CC BY 4.0].

Understanding how repeats expand in the C9orf72 gene is critical to determine how the most common genetic form of ALS develops and progresses.

Sequencing these repeat-rich sequences is a key first step. But charting this repeat-rich region of the C9orf72 gene in people with ALS can be tricky due to its GC-rich nature.

Now, a research team led by Leonard Petrucelli and John Fryer at the Mayo Clinic in Jacksonville, Florida report that long-range next sequencing technologies can be used to navigate these expanded sequences in the C9orf72 gene. The approach is one of a growing number of techniques being developed to detect repeat expansions in the C9orf72 gene and estimate their size (see April 2018 news; Sznajder et al., 2018).

The study is published on August 21 in Molecular Neurodegeneration.


To find out about strategies to identify cases of C9orf72 ALS including on the population scale for genome-wide association (GWAS) analysis, check out A New Test for C9orf72 ALS?


Ebbert MTW, Farrugia SL, Sens JP, Jansen-West K, Gendron TF, Prudencio M, McLaughlin IJ, Bowman B, Seetin M, DeJesus-Hernandez M, Jackson J, Brown PH, Dickson DW, van Blitterswijk M, Rademakers R, Petrucelli L, Fryer JD. Long-read sequencing across the C9orf72 ‘GGGGCC’ repeat expansion: implications for clinical use and genetic discovery efforts in human disease. Mol Neurodegener. 2018 Aug 21;13(1):46. [PubMed].

Sznajder ŁJ, Thomas JD, Carrell EM, Reid T, McFarland KN, Cleary JD, Oliveira R, Nutter CA, Bhatt K, Sobczak K, Ashizawa T, Thornton CA, Ranum LPW, Swanson MS. Intron retention induced by microsatellite expansions as a disease biomarker. Proc Natl Acad Sci U S A. 2018 Apr 2. [PubMed].

Further Reading

Suh E, Grando K, Van Deerlin VM. Validation of a Long-Read PCR Assay for Sensitive Detection and Sizing of C9orf72 Hexanucleotide Repeat Expansions. J Mol Diagn. 2018 Aug 20. pii: S1525-1578(18)30116-8. [PubMed].



c9orf72 disease-als disease-ftd next generation sequencing topic-newmethods topic-preclinical
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